Tandem Alkylation-Second-Order Asymmetric Transformation Protocol for the Preparation of Phenylalanine-Type Tailor-Made α-Amino Acids

用于制备苯丙氨酸型定制α-氨基酸的串联烷基化-二级不对称转化方案

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Abstract

In this work, we disclose an advanced general process for the synthesis of tailor-made α-amino acids (α-AAs) via tandem alkylation-second-order asymmetric transformation. The first step is the alkylation of the chiral Ni(II) complex of glycine Schiff base, which is conducted under mild phase-transfer conditions allowing the structural construction of target α-AAs. The second step is based on the methodologically rare second-order asymmetric transformation, resulting in nearly complete precipitation of the corresponding (S(C),R(N),R(C))-configured diastereomer, which can be collected by a simple filtration. The operational convenience and potential scalability of all experimental procedures, coupled with excellent stereochemical outcome, render this method of high synthetic value for the preparation of various tailor-made α-AAs.

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